1Alrushud AS, et al. BMJ Open 2017;7:e014537. doi:10.1136/bmjopen-2016-014537
Open Access
AbstrActBackground Despite the clinical recommendation of exercise and diet for people with knee osteoarthritis (OA), there are no systematic reviews synthesising the effectiveness of combining physical activity and dietary restriction interventions on the musculoskeletal function of overweight and obese older adults with knee OA.Objective To evaluate the effectiveness of combined physical activity and dietary restriction programmes on body weight, body mass index (BMI) and the musculoskeletal function of overweight and obese older adults with knee OA.Information sources A detailed search strategy was applied to key electronic databases (Ovid, Embase, Web of Science andCumulative Index to Nursing and Allied Health Literature (CINAHL)) for randomised controlled trials (RCTs) published in English prior to 15 January 2017.Participants Participants with BMI ≥25 kg/m2, aged ≥55 years of age and with radiographic evidence of knee OA.Interventions Physical activity plus dietary restriction programmes with usual care or exercise as the comparators.Outcome measures Primary outcome measures were body weight, BMI or musculoskeletal function. Secondary outcome measures were pain and quality of life.Results One pilot and two definitive trials with n=794 participants were included. Two articles reporting additional data and outcome measures for one of the RCTs were identified. All included RCTs had an unclear risk of bias. Meta-analysis was only possible to evaluate mobility (6 min walk test) at 6 months and the pooled random effect 15.05 (95% CI −11.77 to 41.87) across two trials with n=155 participants did not support the combined intervention programme. Narrative synthesis showed clear differences in favour of a reduced body weight and an increased 6 min walk in the intervention group compared with control groups.Conclusion The quality of evidence of benefit of combining exercise and dietary interventions in older overweight/obese adults with knee OA is unclear.
Trail registration number CRD42015019088 and ISRCTN, ISRCTN12906938.
IntroductIonrationaleCurrent evidence shows that the burden of chronic musculoskeletal conditions especially osteoarthritis (OA) increases with advancing age.1 OA is the most common type of arthritis affecting older adults. It is a degenerative joint disease that may affect any joint within the body causing chronic pain, functional limita-tion and emotional disturbance and may lead to disability and negatively affect quality of life (QOL).2–5 Knee OA is a common condi-tion in older adults affecting about 3.64% of the global population in 2010.6 7 In the UK, there is approximately 4.7 million older adults aged 45 years or over experiencing
Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis
Asma S Alrushud,1,2 Alison B Rushton,1,3 Archontissa M Kanavaki,1,3 Carolyn A Greig1,3
to cite: Alrushud AS, Rushton AB, Kanavaki AM, et al. Effect of physical activity and dietary restriction interventions on weight loss and the musculoskeletal function of overweight and obese older adults with knee osteoarthritis: a systematic review and mixed method data synthesis. BMJ Open 2017;7:e014537. doi:10.1136/bmjopen-2016-014537
Received 7 October 2016Revised 24 March 2017Accepted 5 April 2017
1School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK2Department of Health Rehabilitation Sciences, King Saud University, Riyadh, Saudi Arabia3MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research, University of Birmingham, Birmingham, UK
Correspondence toAsma S Alrushud; asa314@ student. bham. ac. uk
Research
Strengths and limitations of this study
► This is the first systematic review of combined physical activity and dietary restriction interventions in overweight and obese older adults with knee osteoarthritis.
► The protocol of this review was registered in PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane handbook; Grading of Recommendation, Assessment, Development and Evaluation was used to evaluate the quality of the included trials.
► The review included a mixed method analytical approach.
► Few eligible studies were identified; however, important information is highlighted which could inform clinical practice.
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knee OA symptoms.1 8 In addition, more than 20 million people seek treatment for knee OA in the USA.9 10 Given the increasing numbers of older adults in the population, combined with the increasing prevalence of obesity and being overweight throughout the population, it is antici-pated that the incidence of knee OA will increase rapidly over the next decade.8
Unfortunately, there is no specific treatment for knee OA. Most recommendations describe three treatment modalities: non-pharmacological, pharmacological and surgical.11 12 Most knee OA evidence-based guide-lines recommend non-surgical treatment13 14 and most general practitioners prefer the non-pharmacological and non-surgical interventions as the first line of treat-ment (recognised as ‘usual care’).11 These interventions are focused on patient education, self-management, pain reduction, function and QOL improvement, body weight reduction and exercise (either land-based or water-based).1 14–17 It is well known that obesity is an important risk factor for knee OA progression and several studies recommend obesity control for decreasing disease burden, since a decrease in body weight will lead to a reduction of joint load and inflammation.3 14 17 18 Weight reduction could be considered as a functional treatment in knee OA rehabilitation since a 12%–15% reduction compared with initial body weight has been shown to improve function and reduce pain.19 Moreover, the appropriate percentage of body weight reduction has been investigated in a systematic review and meta-anal-ysis of five randomised controlled trials (RCTs).20 The review concluded that professional treatment of knee OA should include a weight reduction plan and patients should be encouraged to lose at least 5% of body weight over a 20-week period to achieve symptomatic relief.20
In addition to weight reduction, clinical guidelines for knee OA management and level 1 evidence recom-mend exercise therapy as the main intervention.20–24 Moderate intensity aerobic exercise (eg, walking) is recommended to maintain musculoskeletal function and reduce pain.20–22 However, the optimal exercise prescrip-tion for older adults is still unclear and further research is required.7 The demand for optimal exercise is increased in patients with obesity who may face more challenges and believe in the greater importance of physical activity compared with dietary intervention.25 26
Clinically combining a weight loss programme with exercise therapy may help overweight and obese older adults with knee OA to achieve a 10% loss of total body weight as well as safely relieve knee OA symptoms.3 Also, a recent RCT which included older adults has shown that a non-surgical treatment programme had longer-lasting beneficial effects, evidenced by a delayed requirement for elective total knee replacement (TKR) surgery in a secondary healthcare setting.27 Moreover, for those who are eligible for unilateral TKR, non-sur-gical intervention may delay their surgical intervention for several months.28 There are no systematic literature reviews synthesising the evidence of the effectiveness of
combining physical activity and dietary restriction inter-ventions on the musculoskeletal function of overweight and obese older adults with knee OA.
The aim of this review was to evaluate the effective-ness of combined physical activity and dietary restriction programmes on the musculoskeletal function of over-weight and obese older adults with body mass index (BMI) ≥25 kg/m2, aged ≥55 years of age and with radio-graphic evidence of knee OA.
objectiveTo evaluate the effectiveness of combined physical activity and dietary restriction programmes on body weight, BMI and the musculoskeletal function of overweight and obese older adults with knee OA.
MethodsProtocol and registrationA systematic review was conducted according to a predefined protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRIS-MA)-P guidelines29 and the Cochrane handbook.30 The review was registered on PROSPERO on 01 April 2015 (CRD42015019088), and is reported in accordance with the PRISMA statement (see online supplementary data).29
eligibility criteriaInclusion criteria
► Older adults (aged ≥55 years, men and women). ► Overweight or obese with BMI ≥25 kg/m2.3
► Radiographic evidence of tibiofemoral OA (unilateral or bilateral), grade I–III (mild to moderate) according to the Kellgren and Lawrence system for knee OA classification.31
Exclusion criteria ► Full article not written in English.
StudiesRandomised controlled trials.
InterventionsCombined physical activity and dietary restriction programmes.
ComparatorsUsual care (including advice or physical activity alone or dietary restriction alone) or exercise (participants received an exercise programme similar to the interven-tion group).
outcome measuresPrimary outcome measures: body weight, BMI, muscu-loskeletal function either self-reported function or objective functional performance measures, also, including mobility, joint range of motion (ROM) and muscle strength.
Secondary outcome measures: pain and QOL.
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Open Access
Table 1 Example of Medline Ovid search strategy 1948 to 10 December 2015
# Searches
1 Physical activity/
2 Physical* adj2 (activity or training or therapy*)
3 (Exercis* or rehabilitation* or treatment*)
4 (Closed kinetic chain* or open kinetic chain* or isokinetic* or isometric* or anaerobic* or muscle* or stretching* or aerobic* or isotonic* or treadmill*or endurance* or walking*) adj1 (exercise*)
5 (Resist* adj2 (exercise* or therapy or training))
6 1 or 2 or 3 or 4 or 5
7 Dietary restriction. mp.
8 Meal replacement.mp.
9 Weight loss/ or weight loss.mp. or intentional weight loss.mp.
10 Caloric Restriction/ or Obesity/ or Body Weight/ or hypo or hypocloric diet/
11 Energy intake/ or adipos*/ or Body Mass Index/ or Overweight/
12 Diet/ or Diet, Carbohydrate-Restricted/ or Diet, Reducing/ or Diet Therapy/ or Diet, Vegetarian/
13 Obesity/ or obesity.mp.
14 ((Low carbohydrate* or low calor* or low fat* or vegetarian*) adj1 (diet*))
15 (Diet adj2 (therapy* or treatment*))
16 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15
17 Aging/
18 Exp aged/
19 (55 adj2 (year* or age* or old*))
20 (old* adj (adult* or people or person* or population* or men or women))
21 (aging* adj (adult* or people or person* or population*or men or women))
22 (elder* or senior* or geriatric* ?enarian or ageing)
23 (age* or aging or old* or elder*) adj1 (musc*))
24 17 or 18 or 19 or 20 or 21 or 22 or 23
25 Pain/ or Knee Joint/ or Knee pain.mp. or Osteoarthritis, knee/
26 Knee osteoarthritis.mp. or Osteoarthritis, knee/
27 (Knee* adj (arthritis or osteoarthritis* or inflammation* or degeneration* or disease or pain*))
28 (radiographic* or symptomatic* or clinical* adj1 (knee osteoarthritis*))
29 25 or 26 or 27 or 28
30 Musculoskeletal function. mp.
31 Muscle function. mp.
32 Body composition/
33 Mobility.mp.
34 (Gait or walking) adj1 (speed)
35 Functional ability.mp.
36 ‘Activity of daily’ living/ or. mp.
37 ‘Quality of life’/
38 Balance.mp.
39 (musculoskeletal adj2(pain or disorder*))
40 (Musc* adj (power or strength or performance or function or weakness))
41 41. 30 or 31 or 32 or 33 or 34 or 35 or 36 or 37 or 38 or 39 or 40
42 6 and 16 and 24 and 29 and 41
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Information sourcesThe search employed sensitive, topic-based strategies designed for each database (to 10 December 2015):
► The Cochrane Library: Controlled Trials Register, NHS Economic Evaluation Database.
► Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Medline, Web of Science.
► Hand searches in key journals and lists of references. ► Unpublished research and grey literature such as
Open Grey. ► Government, official, organisational such as UK
Department of Health, WHO and National Health Service (UK).
► Clinical trials registration, theses abstracts and Google scholar.
searchSearch strategies of predefined search terms were developed and tested for applicability (ASA, and a specialist librarian from the University of Birmingham on 13 February 2015). The definitive search strategy was run by two independent researchers (ASA/AMK, 10 December 2015). Endnote X7 software was used for data management. Search results were imported and duplicates were removed. An example of the Medline Ovid search strategy is presented in table 1. The search was updated on 15 January 2017 to include studies published in 2016 by ASA/AMK and no eligible studies were identified.
study selectionThe eligibility of included studies was independently assessed by two reviewers (ASA/AMK) according to the eligibility criteria. The reviewers screened the results of the search by titles and abstracts, and then full text. A study was considered to be eligible when both reviewers assessed the full text independently and found it to fulfil the eligibility criteria. A third reviewer (CAG) mediated in the case of disagreement. The inter-rater agreement was evaluated using Cohen’s Kappa measure.32
data collectionUsing a standardised form (developed by ASA) based on the Cochrane Consumers and Communication Review Group’s data extraction template,33 two reviewers (ASA/AMK) extracted data independently. A third reviewer (CAG) checked for consistency and clarity.
data itemsItems reported on the data extraction form for each trial included demographic information, methodology, inter-vention details and all specified reported outcomes.
risk of bias in individual trialsThe internal validity of each included trial was assessed using the Cochrane risk of bias assessment tool34 recom-mended by PRISMA.29 All domains of the risk of bias
tool were assessed independently by two reviewers (ASA/CAG). A third reviewer (ABR) mediated in the case of disagreement.
risk of bias across trialsRisk of bias was considered high if the proportion of information from trials with high risk of bias was suffi-cient to affect the interpretation of the results. Risk of bias was considered unclear if most information was from studies with a low or unclear risk of bias, and low if most information was from studies with a low risk of bias.34
summary measuresFollowing data extraction, meta-analysis was possible for one key outcome measure across trials that applied similar interventions and compared with exercise at one assess-ment time-point (6 months). Meta-analysis was conducted using RevMan to assess the effectiveness of a combined intervention programme of diet and exercise on mobility (6 min walk test at 6 months) using the random effects model.35 36 Ninety-five per cent Cls were reported for the summary statistics and the SD was calculated from the SEs and CIs.37 38 Data for the other outcomes were avail-able, but meta-analyses were not possible due to different assessment points or comparators. A modified narrative synthesis was used to present these data.39 40
synthesis of resultsA mixed method analysis was required to synthesise the available data.35–40 For the meta-analysis, no raw data were available, and therefore data analyses were conducted on the final summary statistics reports. SDs were esti-mated from reported SE and CI for all available data.36 Heterogeneity in treatment effects was considered by computation of I2. An analysis of the quality of the inter-ventions was undertaken as the basis for interpretation of heterogeneity.36 37 For the modified narrative synthesis, change scores were used for trials when no other data were available.36–38 Two stages of a narrative synthesis were possible to apply; these comprised the development of a preliminary synthesis of findings of included trials, and an exploration of the relationships within and between trials.39 40
developing a preliminary synthesisA preliminary synthesis was developed using tabulation, textual description, grouping and clusters and data trans-formation. Tables were designed presenting the main characteristics of the eligible studies including eligibility criteria, intervention (number of participants, goal of weight loss, intervention period, setting and brief infor-mation about exercise and diet intervention), comparator, outcome measures and the main findings. Additional tables were used to organise studies with respect to specific outcome measures (primary or secondary) and the comparator group. Results were presented as mean (SD) by converting the continuous data from SEs or CIs to SD.39 40
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Figure 1 Study selection flow diagram.48
exploring the relationships within and between trialsA visual representation of the relationship between study characteristics and results was used to explore the rela-tionships within and between trials.39 40
Additional analysesThe Grading of Recommendation, Assessment, Devel-opment and Evaluation (GRADE) approach was used to evaluate the quality of evidence included in the meta-anal-ysis.41 42 Specific software (GRADEpro) was used.43 This approach provided a system for rating the quality of evidence and determining the strength of recommen-dations for clinical practice guidelines.41 42 It has five components: risk of bias, inconsistency, indirectness, imprecision and publication bias. Quality of evidence was categorised as ‘high’, ‘moderate’, ‘low’ and ‘very low’.41 42 Each RCT evaluated as ‘high’ quality evidence was modi-fied according to five negative and two positive factors.41 42
The Cochrane risk of bias assessment tool was used for this component.34 According to the software, risk of bias was classified as not serious, serious or very serious. The quality of evidence was downgraded by one level if there was a serious limitation or by two levels if the limitation was very serious.41 42 Inconsistency was evalu-ated according to I² statistics. It may be considered low if I²<40%, moderate if I²=30%–60%, substantial if I²=50%–90% and considerable if I²=75%–100%.42 Inconsistency was considered as unserious if the reviewers were able to identify a plausible explanation for the heteroge-neity and the quality of evidence was not downgraded.42 Otherwise, the quality of evidence was downgraded by one or two levels if inconsistency of the results was classi-fied as serious or very serious.42 The quality of evidence was downgraded by one or two levels if there was indi-rectness between the study question and the applicability of the evidence.41
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Imprecision of evidence was downgraded in the presence of the following conditions: first, when the boundaries of the CI crossed the no effect line (threshold is completely within the recommended effect) and second, when the criteria for optimal information size (OIS) were not met.42 The criterion for OIS was that the total number of participants included in a systematic review (calculated from a meta-analysis) was less than the number of participants generated by a conventional sample size calculation for a single adequately powered trial. Imprecision was downgraded by one level if one of these conditions was not met or by two levels if both conditions were not met.41 42
Publication of bias was undetectable or strongly suspected according to GRADE software.43 The selec-tive outcome reporting domain of the Cochrane risk of bias assessment tool was used to evaluate the publication bias.34 42 The quality of evidence was downgraded by one level if the selective outcome reporting domain was eval-uated as unclear without justification or downgraded by two levels if evaluated as high.42
resultsstudy selectionThree RCTs (n=794) were included. One was a pilot trial44 and two were definitive trials: the Arthritis, Diet and Activity Promotion Trial (ADAPT)45 and the Inten-sive Diet and Exercise for Arthritis (IDEA).3 For the ADAPT, there was a main trial report, and two additional articles with further analyses of additional outcome measures.46 47 The trials used two comparators: an exer-cise programme in the pilot study and IDEA trial,3 44 while usual care (healthy lifestyle) was the comparator in ADAPT.45 All of the included trials were conducted by the same group from the USA and published in English. No relevant unpublished studies were identified. The inter-rater agreement of the study selection process was excellent with k=0.82.32 There was one disagreement requiring consultation with the third reviewer (CAG), who was asked to clarify the eligibility of articles reporting the same trials. Specifically, one pilot study by Messier et al 44 44 did not clarify whether it was an external or internal pilot study. The senior author was contacted twice but no response was received. The third reviewer recommended it be treated as an external pilot study as there was nothing to indicate it was an internal pilot study in the article reporting the main trial.45 The study flow diagram is presented in figure 1.48
study characteristicsThe main characteristics of the included trials are presented in table 2.
MethodsIn the pilot trial by Messier et al,44 participants were randomised into two groups, a combined intervention and control group.44 The control group received an exercise programme similar to the intervention group. Messier et
al45 randomised participants into four groups: combined intervention, exercise, diet and a control group. The control group received health education plus telephone contact to obtain information on pain, medication use, illness and hospitalisation.45 Messier et al3 randomised participants into three groups: combined intervention, diet group and exercise group. The exercise-alone group was the control. Duration of the trial was 6 months for the pilot trial44 and 18 months for ADAPT45 and IDEA.3
ParticipantsAll participants were community dwelling, obese older adults with radiographic evidence of knee OA. A total of 794 participants aged 55 years or older were randomised into the included studies. One hundred and fifty-five participants were included in the meta-analysis.
InterventionsThe pilot trial44 and two definitive trials3 45 were conducted by the same group from Wake Forest Univer-sity, Winston-Salem, North Carolina, USA. The goal of weight loss varied from 6.8 kg over 6 months to 10%–15% of total body weight over 18 months of intervention. Outcomes were recorded at three time-points for the pilot trial (baseline, 3 months and 6 months) and for the two definitive trials (baseline, 6 months and 18 months). Exercise duration and frequency were similar in all included trials (1 hour/three times per week). Exercise types were aerobic exercise and resistance training. Prin-ciples from group dynamics and social-cognitive theory were used for behavioural treatment in the diet group in IDEA.3 The diet sessions were graded from intensive (facilitating behavioural changes by using self-regula-tory skills) to transition stage (assisting participants who not reached their weight loss goals in establishing new goals) and maintenance stage (assisting patients who had reached their weight loss goals to maintenance of their weight loss). For the intensive weight loss trial, the daily caloric intake was adjusted according to the rate of weight change between intervention visits (low fat and high vegetable diet). The initial diet plan provided an energy-intake deficit of 800–1000 kcal/day, as predicted by an energy expenditure (estimated resting metabo-lism×1.2 activity factor), of at least 1200 kcal for men and 1100 kcal for women.3
outcome measuresDue to few eligible studies, analysis was based on all of the outcomes of interest (body weight and BMI as well as musculoskeletal function), irrespective of whether they were specified as the primary or secondary outcome in the included trials (see below):
Messier et al44: no primary or secondary outcomes were specified.
Messier et al45: the ADAPT primary outcome was self-re-ported physical function measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Secondary outcomes included weight loss,
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Tab
le 2
D
escr
iptiv
e d
ata
for
the
incl
uded
tria
ls
Tit
le/a
utho
r/ y
ear
Aim
Elig
ibili
ty c
rite
ria
Met
hod
sC
om
par
ato
rO
utco
me
mea
sure
sA
sses
smen
t p
oin
tsR
esul
t
Exe
rcis
e an
d w
eigh
t lo
ss in
ob
ese
old
er
adul
ts w
ith k
nee
OA
: a
pre
limin
ary
stud
y.M
essi
er e
t al
(200
0)44
1) T
o d
eter
min
e if
a co
mb
ined
die
tary
and
ex
erci
se in
terv
entio
n re
sults
in
sig
nific
ant
wei
ght
loss
in
old
er o
bes
e ad
ults
with
kn
ee O
A2)
To
com
par
e th
e ef
fect
s of
exe
rcis
e p
lus
die
tary
th
erap
y w
ith e
xerc
ise
alon
e on
gai
t, s
tren
gth,
kne
e p
ain,
b
iom
arke
rs o
f car
tilag
e d
egra
dat
ion
and
phy
sica
l fu
nctio
n
Incl
usio
nA
ged
≥60
yea
rsB
MI ≥
28 k
g/m
²K
nee
pai
n, r
adio
grap
hic
evid
ence
of k
nee
OA
Sel
f-re
por
ted
phy
sica
l d
isab
ility
Exc
lusi
onS
erio
us m
edic
al
cond
ition
affe
ctin
g sa
fety
Pla
nned
cha
nge
of
abod
e or
ad
mis
sion
to
a nu
rsin
g ho
me
with
in n
ext
6 m
onth
s. U
nab
le t
o w
alk
at le
ast
420
ft in
6 m
in
with
out
assi
stiv
e d
evic
eU
nab
le t
o w
alk
on
trea
dm
ill w
ithou
t as
sist
ive
dev
ice
Cur
rent
par
ticip
atio
n in
an
exe
rcis
e p
rogr
amm
e or
oth
er s
tud
yU
nab
le t
o p
artic
ipat
e or
com
ple
te t
he s
tud
y p
roto
col
Par
ticip
ants
n=24
com
mun
ity-d
wel
ling
obes
e ol
der
ad
ults
Goa
l of w
eigh
t lo
ss15
lb (6
.8 k
g)P
erio
d o
f int
erve
ntio
n6
mon
ths
Set
ting
Uni
vers
ity H
ealth
and
E
xerc
ise
Sci
ence
Cen
tre,
U
SA
Exe
rcis
eC
omb
ined
wei
ght
trai
ning
an
d w
alki
ng p
rogr
amm
e fo
r 1
hour
thr
ee t
imes
per
wee
kD
ieta
ry in
terv
entio
nN
utrit
ion
clas
s 1
hour
/wee
k to
inst
ruct
par
ticip
ants
how
to
mod
ify c
alor
ic in
take
us
ing
cogn
itive
beh
avio
ur
mod
ifica
tion
to c
hang
e d
ieta
ry h
abits
to
r eac
h a
grou
p g
oal o
f an
aver
age
wei
ght
loss
the
n th
ree
grou
p
and
one
ind
ivid
ual s
essi
on
held
per
mon
th
Exe
rcis
e gr
oup
(c
ontr
ol)
Bod
y w
eigh
t, s
elf-
rep
ort
que
stio
nnai
re, p
hysi
cal
per
form
ance
and
gai
t an
alys
isS
ynov
ial fl
uid
bio
mar
kers
(to
tal p
rote
ogly
can
(PG
), ke
rata
n su
lfate
(KS
) and
in
terle
ukin
-1β
(IL-1
β))
Freq
uenc
y an
d in
tens
ity o
f kn
ee p
ain
(Lik
ert
scal
e)D
isab
ility
by
self-
rep
orte
d
phy
sica
l fun
ctio
n us
ing
the
Fitn
ess
Art
hriti
s an
d
Sen
iors
Tria
l 6
min
wal
k te
st a
nd t
imed
st
air
clim
bin
g to
mea
sur e
p
hysi
cal p
erfo
rman
ceK
inet
ics
and
kin
emat
ics
anal
ysis
of g
ait
usin
g m
otio
n an
alys
is a
nd fo
rce
pla
te r
ecor
ded
at
3 an
d
6 m
onth
s
Dat
a re
cord
ed a
t b
asel
ine,
3 a
nd 6
mon
ths
Bod
y w
eigh
t re
duc
ed
sign
ifica
ntly
in d
iet
plu
s ex
erci
se
grou
p c
omp
ared
with
exe
rcis
e gr
oup
with
(p=
0.00
7)W
ithin
gro
up d
iffer
ence
s:Th
e co
mb
ined
inte
rven
tion
grou
p lo
st a
mea
n of
18.
8 lb
(8
.5 k
g) a
t 6
mon
ths
com
par
ed
with
4.0
lb (1
.8 k
g) in
the
ex
erci
se g
roup
(p=
0.01
)N
o st
atis
tical
diff
eren
ces
wer
e fo
und
bet
wee
n gr
oup
s in
sel
f-re
por
ted
per
form
ance
mea
sure
s of
phy
sica
l fun
ctio
n an
d k
nee
stre
ngth
Sta
tistic
ally
sig
nific
ant
imp
rove
men
t in
bot
h gr
oup
s in
se
lf-re
por
ted
dis
abili
ty a
nd k
nee
pai
n in
tens
ity a
nd fr
eque
ncy
and
phy
sica
l per
form
ance
At
6 m
onth
s, t
he c
omb
ined
in
terv
entio
n gr
oup
had
a
sign
ifica
ntly
gre
ater
load
ing
rate
(p
=0.
03) a
nd m
axim
um b
raki
ng
forc
e (p
=0.
01) d
urin
g ga
itN
o st
atis
tical
diff
eren
ces
wer
e fo
und
bet
wee
n gr
oup
s in
kne
e p
ain
scor
esC
once
ntra
tion
leve
l of K
S
dec
reas
ed s
imila
rly in
bot
h gr
oup
s Th
e d
ecre
ase
in IL
-1
corr
elat
ed w
ith jo
int
pai
n (r
=−
0.77
, p=
0.04
3)
Con
tinue
d
on Decem
ber 27, 2019 by guest. Protected by copyright.
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J Open: first published as 10.1136/bm
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Open Access
Tit
le/a
utho
r/ y
ear
Aim
Elig
ibili
ty c
rite
ria
Met
hod
sC
om
par
ato
rO
utco
me
mea
sure
sA
sses
smen
t p
oin
tsR
esul
t
Exe
rcis
e an
d d
ieta
ry
wei
ght
loss
in
over
wei
ght
and
ob
ese
old
er a
dul
ts w
ith k
nee
OA
Mes
sier
et
al(2
004)
45
1) T
o d
eter
min
e w
heth
er
long
-ter
m e
xerc
ise
and
d
ieta
ry w
eigh
t lo
ss a
re m
ore
effe
ctiv
e, e
ither
sep
arat
ely
or in
com
bin
atio
n, t
han
usua
l car
e in
imp
rovi
ng
phy
sica
l fun
ctio
n, p
ain
and
m
obili
ty in
old
er o
verw
eigh
t an
d o
bes
e ad
ults
with
kn
ee O
A
Incl
usio
nA
ged
≥60
yea
rsB
MI ≥
28 k
g/m
²K
nee
pai
n, r
adio
grap
hic
evid
ence
of k
nee
OA
Sel
f-re
por
ted
phy
sica
l d
isab
ility
Exc
lusi
onS
erio
us m
edic
al p
rob
lem
Min
i-M
enta
l Sta
te
Exa
min
atio
n sc
ore
of <
24.3
Inab
ility
to
finis
h 18
mon
ths
stud
yIn
abili
ty t
o w
alk
with
out
assi
stiv
e d
evic
eP
artic
ipat
ion
in a
noth
er
stud
y6-
Rep
orte
d a
lcoh
ol
cons
ump
tion
>14
drin
ks
per
wee
kS
T se
gmen
t d
epre
ssio
n of
at
leas
t 2
mm
at
an e
xerc
ise
leve
l of 4
m
etab
olic
eq
uiva
lent
ta
sks
(ME
TS) o
r le
ss,
hyp
oten
sion
or
com
ple
x ar
rhyt
hmia
dur
ing
exer
cise
Inab
ility
to
com
ple
te t
he
stud
y p
roto
col d
ue t
o fr
ailty
, illn
ess
or o
ther
re
ason
Par
ticip
ants
n=31
6 co
mm
unity
-dw
ellin
g ob
ese
old
er a
dul
tsG
oal o
f wei
ght
loss
5% o
f the
tot
al b
ody
wei
ght
over
18
mon
ths
Per
iod
of i
nter
vent
ion
18 m
onth
sS
ettin
gTh
e C
laud
e D
Pep
per
Old
er
Am
eric
ans
Ind
epen
den
ce
Cen
tre,
Wak
e Fo
rest
U
nive
rsity
, US
AE
xerc
ise
1 ho
ur 3
day
s/w
eek
cons
iste
d o
f an
aero
bic
p
hase
a r
esis
tanc
e-tr
aini
ng
pha
se, a
sec
ond
aer
obic
p
hase
and
a c
ool-
dow
n p
hase
Die
tary
inte
rven
tion
Bas
ed o
n p
rinci
ple
s fr
om t
he
grou
p d
ynam
ics
liter
atur
e an
d s
ocia
l cog
nitiv
e th
eory
; d
ivid
ed in
to t
hree
pha
ses:
in
tens
ive
(mon
ths
1–4)
, tr
ansi
tion
(mon
ths
5–6)
and
m
aint
enan
ce (m
onth
s 7–
18)
Die
tary
wei
ght
loss
plu
s ex
erci
se C
omb
ined
the
ex
erci
se a
nd d
ieta
ry w
eigh
t lo
ss p
rogr
amm
es
Usu
al c
are
heal
thy
lifes
tyle
(con
trol
)E
xerc
ise
grou
pD
ieta
ry w
eigh
t lo
ss
grou
p
Prim
ary
outc
ome
Sel
f-re
por
ted
phy
sica
l fu
nctio
n us
ing
the
Wes
tern
O
ntar
io a
nd M
cMas
ter
Uni
vers
ities
Ost
eoar
thrit
is
Ind
ex (W
OM
AC
)S
econ
dar
y ou
tcom
es
Wei
ght
loss
, 6 m
in w
alk
dis
tanc
e, s
tair-
clim
b t
ime,
W
OM
AC
pai
n an
d s
tiffn
ess
scor
es a
nd jo
int
spac
e w
idth
Dat
a re
cord
ed a
t b
asel
ine,
6 a
nd
18 m
onth
s
Sig
nific
ant
bod
y w
eigh
t lo
ss in
d
iet
grou
ps
(p<
0.05
). D
iet
plu
s ex
erci
se a
nd d
iet
grou
p lo
st a
n av
erag
e of
5.7
% a
nd 4
.9%
of
thei
r b
ody
wei
ght,
res
pec
tivel
y w
ith 1
.2%
for
the
heal
thy
lifes
tyle
gro
upS
igni
fican
t im
pro
vem
ents
in
self-
rep
orte
d p
hysi
cal f
unct
ion
(p<
0.05
), 6
min
wal
k d
ista
nce
(p<
0.05
), st
air-
clim
b t
ime
(p<
0.05
) and
kne
e p
ain
(p<
0.05
) in
the
die
t p
lus
exer
cise
gro
up
com
par
ed w
ith t
he h
ealth
y lif
esty
le g
roup
Sig
nific
ant
imp
rove
men
t in
th
e 6
min
wal
k d
ista
nce
in
the
exer
cise
gro
up (p
<0.
05)
The
die
t-on
ly g
roup
was
not
si
gnifi
cant
ly d
iffer
ent
from
the
he
alth
y lif
esty
le g
roup
with
re
spec
t to
any
of t
he fu
nctio
nal
or m
obili
ty m
easu
res
Cha
nges
in jo
int
spac
e w
idth
w
ere
not
sign
ifica
ntly
diff
eren
t b
etw
een
grou
ps
Tab
le 2
C
ontin
ued
Con
tinue
d
on Decem
ber 27, 2019 by guest. Protected by copyright.
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J Open: first published as 10.1136/bm
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nloaded from
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Open Access
Tit
le/a
utho
r/ y
ear
Aim
Elig
ibili
ty c
rite
ria
Met
hod
sC
om
par
ato
rO
utco
me
mea
sure
sA
sses
smen
t p
oin
tsR
esul
t
Effe
cts
of in
tens
ive
die
t an
d e
xerc
ise
on k
nee
join
t lo
ads,
infla
mm
atio
n an
d
clin
ical
out
com
es
amon
g ov
erw
eigh
t an
d
obes
e ad
ults
with
kne
e O
A is
the
Inte
nsiv
e D
iet
and
E
xerc
ise
for
Art
hriti
s ra
ndom
ised
clin
ical
tria
lM
essi
er e
t al
(201
3)3
To d
eter
min
e w
heth
er a
10
% r
educ
tion
in b
ody
wei
ght
ind
uced
by
die
t, w
ith
or w
ithou
t ex
erci
se, w
ould
im
pro
ve m
echa
nist
ic a
nd
clin
ical
out
com
es m
ore
than
ex
erci
se a
lone
Incl
usio
nA
ged
≥55
yea
rsK
ellg
ren-
Law
renc
e14
gra
de
2 or
3 (m
ild o
r m
oder
ate)
rad
iogr
aphi
c tib
iofe
mor
al O
A o
r tib
iofe
mor
al p
lus
pat
ello
fem
oral
OA
of o
ne
or b
oth
knee
s, p
ain
on
mos
t d
ays
due
to
knee
O
A.
BM
I fro
m 2
7 to
41
Sed
enta
ry li
fest
yle
(<30
min
per
wee
k of
fo
rmal
exe
rcis
e fo
r th
e p
ast
6 m
onth
s)P
artic
ipan
ts u
sual
m
edic
atio
ns c
ould
be
mai
ntai
ned
or
adju
sted
d
epen
din
g on
phy
sici
an
advi
ceE
xclu
sio
nS
igni
fican
t co
mor
bid
d
isea
se t
hat
wou
ld p
ose
a sa
fety
thr
eat
or im
pai
r ab
ility
to
par
ticip
ate,
p
revi
ous
acut
e kn
ee
inju
ry, p
atel
lofe
mor
al
OA
in t
he a
bse
nce
of
tibio
fem
oral
OA
Ab
ility
and
will
ingn
ess
to m
odify
die
tary
or
exer
cise
beh
avio
urs
Exc
ess
alco
hol u
seIn
abili
ty t
o fin
ish
18-m
onth
stu
dy
or
unlik
ely
to b
e co
mp
liant
Con
diti
ons
that
pro
hib
it kn
ee M
RI
Sig
nific
ant
cogn
itive
im
pai
rmen
t or
dep
ress
ion
Par
ticip
ants
n=45
4G
oal o
f wei
ght
loss
10%
–15%
of t
he t
otal
bod
y w
eigh
tP
erio
d o
f int
erve
ntio
n18
mon
ths
Set
ting
Wak
e Fo
rest
Uni
vers
ity
and
Wak
e Fo
rest
Sch
ool o
f M
edic
ine,
US
AIn
tens
ive
wei
ght
loss
in
terv
entio
nTh
e d
iet
incl
uded
up
to
two
mea
l-re
pla
cem
ent
shak
es p
er d
ay F
or t
he
third
mea
l, p
artic
ipan
ts
follo
wed
a w
eekl
y m
enu
pla
n an
d r
ecip
es t
hat
wer
e 50
0–75
0 kc
al, l
ow in
fat
and
hi
gh in
veg
etab
les.
Dai
ly
calo
ric in
take
was
ad
just
ed
acco
rdin
g to
the
rat
e of
w
eigh
t ch
ange
bet
wee
n in
terv
entio
n vi
sits
. The
in
itial
die
t p
lan
pro
vid
ed a
n en
ergy
-int
ake
defi
cit
of 8
00–
1000
kca
l/day
as
pre
dic
ted
b
y en
ergy
exp
end
iture
(e
stim
ated
res
ting
met
abol
ism
×1.
2 ac
tivity
fa
ctor
)Th
e ex
erci
se in
terv
entio
nIt
was
con
duc
ted
for
1 ho
ur o
n 3
day
s/w
eek
for
18 m
onth
s P
artic
ipat
ion
was
cen
tre-
bas
ed fo
r th
e fir
st 6
mon
ths
Aft
er 6
-mon
th
follo
w-u
p t
estin
g an
d a
2-
wee
k tr
ansi
tion
pha
se,
par
ticip
ants
cou
ld r
emai
n in
the
faci
lity
pro
gram
me,
op
t fo
r a
hom
e-b
ased
p
rogr
amm
e or
com
bin
e th
at t
wo.
The
pro
gram
me
cons
iste
d o
f aer
obic
wal
king
(1
5 m
in),
stre
ngth
tra
inin
g (2
0 m
in),
a se
cond
aer
obic
p
hase
(15
min
) and
coo
l-d
own
(10
min
)
Exe
rcis
e gr
oup
(c
ontr
ol g
roup
)D
ieta
ry w
eigh
t lo
ss
grou
p
Prim
ary
outc
omes
kn
ee jo
int
com
pre
ssiv
e fo
rce
and
pla
sma
IL-6
co
ncen
trat
ion
Sec
ond
ary
clin
ical
ou
tcom
esS
elf-
rep
orte
d p
ain
(ran
ge
0–20
), fu
nctio
n (r
ange
0–
68),
mob
ility
and
hea
lth-
rela
ted
qua
lity
of li
fe
Par
ticip
ants
wer
e as
sess
ed a
t b
asel
ine,
6
and
18
mon
ths
Bod
y w
eigh
t w
as r
educ
ed
sign
ifica
ntly
in b
oth
die
t gr
oup
s (d
iet
and
die
t p
lus
exer
cise
) m
ore
than
exe
rcis
e gr
oup
(p
<0.
001)
With
in g
roup
diff
eren
ces:
the
die
t p
lus
exer
cise
gro
up lo
st
abou
t 10
.6 k
g (1
1.4%
), th
e d
iet
grou
p lo
st 8
.9 k
g (9
.5%
) and
1.
8 kg
(2.0
%) o
f bas
e lin
e b
ody
wei
ght
No
sign
ifica
nt d
if fer
ence
in
wal
king
sp
eed
and
6 m
in w
alk
test
bet
wee
n gr
oup
sS
igni
fican
t p
ain
red
uctio
n w
as o
bse
rved
in t
he d
iet
plu
s ex
erci
se g
roup
at
18 m
onth
s co
mp
ared
with
exe
rcis
e gr
oup
(m
ean
scor
e, 1
.02;
95%
CI 0
.33
to 1
.71;
p=
0.00
4)Th
e d
iffer
ence
in t
he S
F-36
(36-
item
sho
rt fo
rm s
urve
y) p
hysi
cal
sub
scal
e w
as 2
.81
units
in
die
t p
lus
exer
cise
rel
ativ
e to
ex
erci
se g
roup
(95%
CI −
4.76
to
−0.
86; p
=0.
005)
No
sign
ifica
nt d
if fer
ence
in
the
men
tal s
ubsc
ale
bet
wee
n gr
oup
s
QA
,ost
eoar
thrit
is.
Tab
le 2
C
ontin
ued
on Decem
ber 27, 2019 by guest. Protected by copyright.
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Open Access
Table 3 Summary assessment of the overall risk of bias for each trial
Study (author, year)
Component of risk of bias
Summary risk of bias1 2 3 4 5 6
Messier et al, 200044 U U U U L U Unclear (5) Low (1)
Rejeski et al, 200246 U U U L L U Unclear (4) Low (2)
Messier et al, 200445 L U U L L U Unclear (3) Low (3)
Focht et al, 200547 U U U L L U Unclear (4) Low (2)
Messier et al, 20133 L U U L L U Unclear (3) Low (3)
Figure 2 6 min walk test (metres) at 6 months.
6 min walk distance, stair-climb time, WOMAC pain and stiffness scores and joint space width.45
Messier et al3: in the IDEA trial, the primary outcomes were knee joint compressive force and plasma inter-leukin (IL)-6 concentration. Secondary outcome measures included WOMAC pain, WOMAC function, gait speed, 6 min walk test, QOL, body weight, height, BMI and body composition.3
risk of bias within trialsSubstantial inter-reviewer agreement was achieved on the risk of bias assessment (k=0.73).32 All of the included trials were evaluated as unclear risk of bias.34 Most of the key domains were assessed as unclear risk of bias within each trial (table 3).
risk of bias across trialsRisk of bias across trials was evaluated as unclear,34 only component 5 (selective outcome reporting) was evalu-ated as low risk of bias for all studies. For the ‘blinding of participants, personnel and outcome assessor’ compo-nent, all trials were evaluated as having unclear risk of bias as no strategies were reported to address the issue of outcome assessor unblinding. Also, for the ‘other sources of bias’ components, all trials were evaluated with unclear risk of bias due to unclear reporting.
results of individual trials and synthesis of resultsQuantitative synthesisMeta-analysis was possible for only one outcome measure at one assessment time-point. Meta-analysis was used to assess the effect of the combined intervention programme compared with exercise on the 6 min walk test (metres) after 6 months of intervention. Only two trials3 44 with unclear risk of bias with n=155 participants were available for meta-analysis. The pooled random effects (15.05, 95% CI −11.77 to 41.87) did not support a combined intervention effect (figure 2).
synthesis of resultsModified narrative synthesisWith respect to the guidelines for a narrative synthesis, only two elements were possible to apply: developing a preliminary synthesis and exploring the relationships within and between studies.39 40
Developing a preliminary synthesisTabulation was used to present primary and secondary outcome measures that were not included in the meta-analysis: body weight, knee ROM, physical function, mobility, pain and QOL. Studies including a comparison of the combined intervention programme with an exer-cise intervention are presented in tables 4-5.
Tabulation was used to compare the effect of the combined intervention programme compared with usual care (healthy lifestyle) on primary and secondary outcome measures: body weight, physical function, mobility, pain and QOL (tables 6-7).
Exploring the relationships within and between studiesCharacteristics of the trials are presented in table 2. All included trials were conducted by the same research group. The eligibility criteria were very similar across studies. The exercise intervention included strength-ening and aerobic exercise. The intervention frequency (1 hour/three times per week) was the same across the included trials. Further details about the design of the trials are presented above.
Tables 4 and 6 show differences between the inter-vention group and the control group (despite the comparator) with respect to body weight and the 6 min walk distance. These differences were consistent with the results from the included trials. The diet plus exer-cise group in the pilot study44 lost weight compared with the control group (p=0.01) after 6 months of inter-vention44 and this was also the case with respect to the
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jopen-2016-014537 on 8 June 2017. Dow
nloaded from
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Open Access
Tab
le 4
P
relim
inar
y sy
nthe
sis
for
the
prim
ary
outc
ome
mea
sure
s at
bas
elin
e an
d a
fter
inte
rven
tion:
bod
y w
eigh
t, k
nee
RO
M, p
hysi
cal f
unct
ion
and
mob
ility
com
par
ing
the
com
bin
ed in
terv
entio
n p
rogr
amm
e w
ith a
n ex
erci
se in
terv
entio
n
Cat
ego
ryO
utco
me
mea
sure
Ass
essm
ent
po
int(
mo
nths
)S
tud
y
Inte
rven
tio
n g
roup
Co
ntro
l gro
up
M0
(SD
0)N
0M
1(S
D1)
N1
M0
(SD
0)N
0M
1(S
D1)
N1
Bod
y w
eigh
tB
ody
wei
ght
(kg)
6M
essi
er e
t al
, 200
04491
(13)
1382
.5 (4
)12
109
(17)
1110
7.2
(15)
9
6M
essi
er e
t al
, 201
3393
(14.
7)15
284
.3 (1
4.7)
133
92.3
(14.
6)15
092
.4 (1
5.4)
122
18M
essi
er e
t al
, 201
3393
(14.
7)15
282
.4 (1
5.2)
121
92.3
(14.
6)15
090
.5 (1
5)11
5
Kne
e R
OM
RO
M6
Mes
sier
et
al, 2
00044
55.2
7* (N
/A)
1356
.47
(0.9
1)12
55.2
7* (N
/A)
1156
.73
(1.0
2)9
Est
imat
ed c
once
ntric
ex
tens
ion
(deg
ree)
6M
essi
er e
t al
, 200
04430
.7 (N
/A)
1331
(N/A
)12
30.7
(N/A
)11
33.4
(N/A
)9
Est
imat
ed c
once
ntric
flex
ion
6M
essi
er e
t al
, 200
04418
.2 (N
/A)
1318
.5 (N
/A)
1218
.2 (N
/A)
1120
.8 (N
/A)
9
Phy
sica
l fu
nctio
n P
hysi
cal f
unct
ion
(WO
MA
C)
18M
essi
er e
t al
, 201
3324
.6 (1
1.7)
152
14.2
(10.
4)12
123
.1 (1
0.3)
150
17.6
(9.8
)11
5
Mob
ility
6 m
in w
alk
test
(m)
18M
essi
er e
t al
, 201
3346
7 (8
7.9)
152
537
(92.
6)12
148
0 (9
0.3)
150
525
(79.
2)11
5
Sta
ir cl
imb
(s)
6M
essi
er e
t al
, 200
0449.
81*
137.
4 (0
.32)
129.
81*
118.
7 (0
.36)
9
M0
(SD
0), m
ean
and
SD
at
bas
elin
e; N
0, p
artic
ipan
ts n
umb
er a
t b
asel
ine;
M1
(SD
1), m
ean
and
SD
aft
er in
terv
entio
n; N
1; p
artic
ipan
ts n
umb
er a
fter
inte
rven
tion;
N/A
, dat
a no
t av
aila
ble
.
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Open Access
Tab
le 5
P
relim
inar
y sy
nthe
sis
for
the
seco
ndar
y ou
tcom
e m
easu
res
at b
asel
ine
and
aft
er in
terv
entio
n: b
ody
wei
ght,
pai
n an
d Q
OL
com
par
ing
the
com
bin
ed in
terv
entio
n p
rogr
amm
e w
ith a
n ex
erci
se in
terv
entio
n
Cat
ego
ryA
sses
smen
t p
oin
t(m
ont
hs)
Out
com
e m
easu
reS
tud
y
Inte
rven
tio
n g
roup
Co
ntro
l gro
up
M0
(SD
0)N
0M
1 (S
D1)
N1
M0
(SD
0)N
0M
1 (S
D1)
N1
Pai
nW
OM
AC
pai
n6
Mes
sier
et
al, 2
0133
6.7
(3.4
)15
24.
6 (2
.9)
133
6.1
(2.9
)15
04.
5 (3
)12
2
WO
MA
C p
ain
18M
essi
er e
t al
, 201
336.
7 (3
.4)
152
3.7
(3.1
)12
16.
1 (2
.9)
150
4.4
(2.7
)11
5
QO
LS
F-36
phy
sica
l com
pon
ent
6M
essi
er e
t al
, 201
3336
.6 (9
.41)
152
43.5
(9)
133
36.8
(9)
150
41.5
(9)
122
SF-
36 m
enta
l com
pon
ent
6M
essi
er e
t al
, 201
3357
.2 (6
.6)
152
56.9
(7.3
)13
356
.5 (8
.4)
150
56.1
(7.6
)12
2
SF-
36 p
hysi
cal c
omp
onen
t18
Mes
sier
et
al, 2
0133
36.6
(9.4
1)15
244
.7 (8
.7)
121
36.8
(9)
150
42.0
(9)
115
SF-
36 m
enta
l com
pon
ent
18M
essi
er e
t al
, 201
3356
.1 (6
.5)
152
57.2
(6.6
)12
156
.5 (8
.4)
150
55.4
(7.6
)11
5
M0
(SD
0), m
ean
and
SD
at
bas
elin
e; N
0, p
artic
ipan
ts n
umb
er a
t b
asel
ine;
M1
(SD
1), m
ean
and
SD
aft
er in
terv
entio
n; N
1, p
artic
ipan
ts n
umb
er a
fter
inte
rven
tion;
N/A
, dat
a no
t av
aila
ble
.
longer duration intervention trial (18 months) in which the intervention group lost significantly (p <0.001) more weight than the exercise group.3 However, in ADAPT45 both groups (intervention and healthy lifestyle) lost weight (p<0.05) after 18 months of intervention,45 although there was a significant difference in the 6 min walk result in favour of the diet plus exercise group (p<0.05).45 Also, there was a significant difference (p=0.005) in the 6 min walk between the intervention and exercise groups in the IDEA trial.3
Additional analysisNo further analyses were possible owing to the lack of reported information and low number of included trials.
Grading the quality of evidenceA summary assessment was undertaken to draw conclusions about the overall quality of evidence for the combined intervention on mobility using GRADE software.43 Both trials included in the meta-analysis3 44 were evaluated as ‘high’ quality evidence before being downgraded as they were RCTs, before being modified according to five nega-tive and two positive factors.41 42 The quality of evidence for a combined intervention programme of physical activity and diet on walking distance (metres) within 6 min after a period of 6 months of intervention was eval-uated as moderate (table 8).
dIscussIonsummary of evidenceThis is the first systematic review and mixed method anal-ysis investigating the effectiveness of combining dietary restriction and physical activity interventions for muscu-loskeletal function in overweight/obese older adults with knee OA. One pilot trial44 and two definitive trials3 45 (794 participants) conducted by the same research group (Wake Forest University) were included. The interven-tion programme was compared with exercise training in one definitive trial (IDEA)3 and the pilot trial,44 while usual care was the comparator in the ADAPT.45 Two addi-tional articles46 47 which reported further outcomes of the ADAPT were identified.45
Data syntheses of this review were conducted using both meta-analysis and modified narrative synthesis. Although visual inspection of the tables of results indi-cated that the combined programme enhanced body weight reduction, and improved mobility, there was moderate evidence for no effect. Changes of BMI scores were not reported in the included studies. Meta-analysis was possible for only the 6 min walk test at 6 months and was not possible for the other outcome measures due to the inconsistency of assessment points or the compar-ator. The pooled random effect of two trials3 44 with 155 participants did not support the combined intervention programme (15.05, 95% CI −11.77 to 41.87) (although with a total effect of 15 m deemed not clinically signif-icant according to previous literature).49 50 Although the meta-analyses showed substantial heterogeneity
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Open Access
Tab
le 6
P
relim
inar
y sy
nthe
sis
for
the
prim
ary
outc
ome
mea
sure
s at
bas
elin
e an
d a
fter
inte
rven
tion:
phy
sica
l fun
ctio
n an
d m
obili
ty c
omp
arin
g th
e co
mb
ined
inte
rven
tion
pro
gram
me
with
usu
al c
are
Cat
ego
ryO
utco
me
mea
sure
Ass
essm
ent
po
int
(mo
nths
)S
tud
y
Inte
rven
tio
n g
roup
Co
ntro
l gro
up
M0
(SD
0)N
0M
1 (S
D1)
N1
M0
(SD
0)N
0M
1 (S
D1)
N1
Bod
y w
eigh
tB
ody
wei
ght
(kg)
18M
essi
er e
t al
, 200
44592
(1.7
)76
86.8
(N/A
)58
96 (1
.8)
7894
.9 (N
/A)
67
Phy
sica
l fu
nctio
nP
hysi
cal f
unct
ion
(WO
MA
C)
6M
essi
er e
t al
, 200
44523
.6 (1
2.2)
7617
.9*
(N/A
)63
26 (1
1.4)
7822
.4*
(N/A
)70
Phy
sica
l fun
ctio
n (W
OM
AC
)18
Mes
sier
et
al, 2
00445
23.6
(12.
2)76
29.3
* (N
/A)
5826
(11.
4)78
29.4
(N/A
)67
Mob
ility
6 m
in w
alk
test
(m)
6M
essi
er e
t al
, 200
44541
6.2
(98.
7)76
482.
3 (1
00)
6343
4.6
(96.
4)78
429
(108
)70
6 m
in w
alk
test
(m)
18M
essi
er e
t al
, 200
44541
6.2
(98.
7)76
477.
8 (9
9.7)
5843
4.6
(96.
4)78
429.
9 (1
04.7
)67
6 m
in w
alk
test
(m)
18Fo
cht
et a
l, 20
0547
414.
5 (8
5.3)
N/A
465
(96.
3)N
/A43
3.4
(81.
9)N
/A43
0 (7
9.5)
N/A
Sta
ir cl
imb
(s)
6M
essi
er e
t al
, 200
44510
.9 (5
.8)
768.
8 (6
.2)
639.
5 (5
.6)
789.
9 (6
.3)
70
Sta
ir cl
imb
(s)
18Fo
cht
et a
l, 20
0547
10.4
(7.3
)N
/A8.
9 (5
.4)
NA
9.4
(4.9
)N
/A9.
9 (5
.6)
N/A
*Est
imat
ed v
alue
from
figu
re 2
in r
ef. 4
5.M
0 (S
D0)
, mea
n an
d S
D a
t b
asel
ine;
N0,
par
ticip
ants
num
ber
at
bas
elin
e; M
1 (S
D1)
, mea
n an
d S
D a
fter
inte
rven
tion;
N1,
par
ticip
ants
num
ber
aft
er in
terv
entio
n; N
/A, d
ata
not
avai
lab
le.
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Open Access
Tab
le 7
P
relim
inar
y sy
nthe
sis
for
the
seco
ndar
y ou
tcom
e m
easu
res
at b
asel
ine
and
aft
er in
terv
entio
n: b
ody
wei
ght,
pai
n an
d Q
OL
com
par
ing
the
com
bin
ed in
terv
entio
n p
rogr
amm
e w
ith u
sual
car
e
Cat
ego
ryO
utco
me
mea
sure
Ass
essm
ent
po
int
(mo
nths
)S
tud
y
Inte
rven
tio
n g
roup
Co
ntro
l gro
up
M0
(SD
0)N
0M
1 (S
D1)
N1
M0
(SD
0)N
0M
1 (S
D1)
N1
Pai
nP
ain
scal
e (W
OM
AC
)6
Mes
sier
et
al, 2
00445
7.3
(3.6
)76
5.5
(3.7
)63
7.3
(3.4
)78
6.2
(3.9
)70
Pai
n sc
ale
(WO
MA
C)
18M
essi
er e
t al
, 200
4457.
3 (3
.6)
765.
1 (3
.6)
587.
3 (3
.4)
786
(3.7
)67
QO
LS
F-36
phy
sica
l co
mp
onen
t
Ave
rage
of 6
and
18
Rej
eski
et
al.,
2002
4635
.39
(10.
5)68
40.5
7 (N
/A)*
N/A
33.6
0 (8
.4)
6840
.57
(N/A
)*N
/A
SF-
36m
enta
l co
mp
onen
t
Ave
rage
of 6
and
18
Rej
eski
et
al.,
2002
4652
.85
(10.
7)68
53.5
1 (N
/A)*
N/A
52.7
0 (1
0.9)
6853
.31
(N/A
)*N
/A
M0
(SD
0), m
ean
and
SD
at
bas
elin
e; N
0, p
artic
ipan
ts n
umb
er a
t b
asel
ine;
M1
(SD
1), m
ean
and
SD
aft
er in
terv
entio
n; N
1, p
artic
ipan
ts n
umb
er a
fter
inte
rven
tion;
N/A
, dat
a no
t av
aila
ble
, *, o
nly
SE
M d
ata
avai
lab
le; S
D1
dat
a co
uld
not
be
calc
ulat
ed d
ue t
o m
issi
ng N
1 va
lue.
I²=50%, this was classified as not serious using the GRADE evaluation tool41 42 as it was assessed as likely to be due to high variability in both the sample size and effect size. Clinical heterogeneity across trials was limited to comparator and duration. Overall, the quality of evidence was downgraded to moderate due to imprecision of the results according to GRADE.43 All included trials were reported as having an unclear risk of bias, which was mainly due to unclear reporting of some information.34 For instance, both the ‘blinding of participants, personnel and outcome assessor’ and the ‘other sources of bias’ component were evaluated as unclear for all trials.
Results from the trial by Messier et al44 indicated no statistically significant differences across groups with regard to self-reported performance measures of physical function, knee pain scores, knee strength and biomechanical measures (synovial fluid, keratan sulfate and level of IL-1) after 6 months of intervention. Findings from Messier et al45 indicated a statistically significant benefit of the combined intervention in terms of self-reported physical function, 6 min walk test, stair climb and knee pain. The findings from Messier et al3 indicated a significant improvement in the 6 min walk test and walking speed in the intervention group. Moreover, there was a significant reduction (p<0.05) of body weight among the intervention groups in all trials. In the current review, the finding of no effect of a combined intervention programme may be due to the very low number of included trials (and participants) but probably is not due to low compliance. Compli-ance of the diet and exercise group to the exercise programme at 6 months was higher in the pilot study44 compared with the IDEA trial.3 In the pilot study,44 compliance (ratio of the number of exercise sessions attended to the total number of the exercise sessions prescribed with the exercise programme) was 82.6% for the exercise group and 94.7% for diet plus exercise group. For the IDEA trial,3 399/454 participants (88%) completed the study; compliance of the diet and exer-cise group was 70% at 6 months and 58% at 18 months with no adverse events and no significant differences between groups.
In addition to diet and exercise, two current trials MEDIC128 and MEDIC227 have reported that a multimodal approach of education, neuromuscular exercise, insoles and, if indicated, a dietary weight loss programme and pain medication are effective for adults and older adults with moderate-to-severe knee OA. These studies were not included in this review due to the wide age range across participants. MEDIC128 included 9 participants and MEDIC227 included 12 participants below the age of 55 years and there was no subgroup analysis of older participants. In MEDIC1,28 the participants were eligible for TKR and were randomised to non-surgical and surgical treat-ment followed by the intervention programme. Both interventions showed substantial improvement, but the
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Open Access
Table 8 Factors determining the quality of evidence according to GRADE
Factor Judgement Explanation
1. Risk of bias Not serious ►Only two studies included in meta-analysis and both of them evaluated as unclear risk of bias ►No serious limitations to downgrade the quality of evidence ►Sequence generation was not reported in one study; allocation concealment not specified in both studies; no strategy reported to address issue of outcome assessor unblinding ► Incomplete outcome data evaluated as ‘unclear’ in the pilot study; no mention of missing data or methods used to address missing data; no primary outcome stated for the pilot study
2. Inconsistency Not serious ► I²=50%, which may be evaluated as either low or substantial heterogeneity; this overlap affects the decision making ►Magnitude of heterogeneity could be the result of high variability in the sample size and effect size which justifies the decision
3. Indirectness Not serious ►Direct applicability of the included studies aims and objectives to their target populations, interventions and outcomes of interest
4. Imprecision Serious ►Boundaries of CI crossing the no effect line which downgrades the quality of evidence by one level ►Number of participants needed for a single powered trial is higher than number of participants estimated from the meta-analysis; quality of evidence not downgraded on this basis
5. Publication bias
Undetected ►Selective outcome reporting domain evaluated low in both studies; publication bias considered as not serious by two reviewers
surgical treatment resulted in greater pain relief and functional improvement after 12 months compared with non-surgical treatment alone. However, only 26% of the patients who were assigned to receive non-sur-gical treatment alone underwent TKR in the following year.28 In MEDIC2,27 participants had radiographic confirmation of OA (Kellgren-Lawrence grade ≥1), but were not eligible for a TKR. The 12-week non-sur-gical treatment programme consisted of individualised progressed neuromuscular exercise, patient educa-tion, insoles, dietary advice and prescription of pain medication if indicated, while usual care comprised two leaflets with information and advice on knee OA and recommended treatments. This non-surgical treat-ment programme was found to be more effective with respect to pain, activities of daily living and QOL at 12 months compared with usual care, although it was not possible to determine which of the components within this multi-intervention programme were most effec-tive and whether the intervention as a whole would be equally effective in older patients with OA.27
The main limitation of this review is that only few eligible studies were identified. Thus, the optimal compo-nents of dietary and exercise interventions in terms of type, duration and quantity suitable for this population are still unclear. Future studies are required in this field to optimise outcome measures and methods of delivering a programme at an acceptable cost, prior to a future adequately powered definitive trial.
conclusionBased on current evidence synthesised in this review, it is hard to judge the effectiveness of a combined programme of diet and physical activity due to the low number of included trials and participants and the quality of available evidence. Only moderate quality evidence was available to investigate the intervention programmes. However, the narrative synthesis suggests that interventions with a focus on reduction of body weight and/or improved mobility are worthy of further evaluation. Further adequately powered RCTs testing the effects of a combined interven-tion against each component individually are required to optimise diet and exercise interventions using a multi-modal approach.Correction notice This paper has been amended since it was published Online First. Owing to a scripting error, some of the publisher names in the references were replaced with 'BMJ Publishing Group'. This only affected the full text version, not the PDF. We have since corrected these errors and the correct publishers have been inserted into the references.
Acknowledgements The authors would like to thank Lynn Harris, Library Services, University of Birmingham for her contribution to the development of the search strategies.
Contributors ASA led the review and contributed to all stages, including development of the search strategy, running the searches, assessing trials eligibility, data extraction and synthesis (including risk of bias and Grading of Recommendation, Assessment, Development and Evaluation analysis), and preparation of the manuscript. CAG and ABR provided expertise in systematic review methodology and risk of bias analysis. AMK assisted with assessment of eligibility of included studies and data extraction. All authors read and provided feedback on the preparation of this manuscript according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 checklist and approved the final manuscript.
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Open Access
Funding This review is a part of a PhD programme undertaken by ASA, and is fully funded by the King Saud University, Kingdom of Saudi Arabia, Riyadh and the Saudi Arabian Cultural Bureau, United Kingdom, London.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement There are no additional unpublished data from the review.
Open Access This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/
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